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Immunotherapy agent showed high response rates in three tumor types
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CHICAGO — Treatment with the investigational drug BMS-936558 induced tumor shrinkage in up to 25% of patients with advanced melanoma, kidney and non–small cell lung cancers, according to results of an early-stage study.
Following up on prior data in which blockade of programmed death-1 (PD-1) overcame immune resistance and mediate tumor regression, Suzanne Topalian, MD, of Johns Hopkins University School of Medicine, and colleagues examined the activity and safety of BMS-936558, a fully human monoclonal antibody blocking PD-1, as a possible target for cancer therapy.
In this phase I trial, researchers enrolled 296 patients with melanoma, colorectal, NSCLC, prostate and renal cancer that had progressed despite standard therapies. They administered BMS-936558 IV once every 2 weeks at doses of 0.1 mg/kg to 10 mg/kg during dose-escalation and/or cohort expansion. As of July 1, 2011, 240 patients with melanoma (n=95), renal cell (n=33), colorectal (n=19), NSCLC (n=75), prostate (n=17) cancer and unknown (n=1) were treated.
Responses were observed in patients with melanoma (28%), renal cancer (27%) and NSCLC (18%) — responses were observed in patients with squamous and non-squamous cell subtypes of lung cancer. Notable adverse effects included pneumonitis, hypophysitis, hepatitis, colitis and thyroiditis.
“Serious side effects were encountered in 14% of patients, with many of these side effects consistent with an immune-related causality as you might expect if you released the brakes on immune responses — as we’re seeing antitumor responses, we might also see immune-related side effects” Topalian said during a press conference. “We did see three treatment-related deaths in the total patient population due to pneumonitis or lung inflammation, which we believe has an immune-related etiology. Over the course of time, we have developed better ways to identify people who are at-risk for this side effect, as well as better ways to detect it early on and treat it aggressively.”
A subanalysis of data from the trial also suggests that PD-1 ligand (PD-L1) could represent a potential biomarker on cancer cells that could help predict which patients will respond to BMS-936558. Researchers analyzed tumor samples obtained from 42 patients before treatment initiation, for expression of the PD-L1 protein on the surface of tumor cells. After comparing the results with response data, researchers said more than one-third of patients with PD-L1–positive tumors responded to the drug (36%), whereas none of the 17 PD-L1–negative patients exhibited a response.
“It is important to note, only 5% of all patients treated in this trial have discontinued treatment due to related side effects. So, in general, treatment was well tolerated in an outpatient setting and the side effects were manageable,” Topalian said. “Based on these study results, anti-PD-1 antibody BMS-936558 can be administered safely in an outpatient setting to heavily pretreated patients with durable clinical benefit in patients with lung cancer, melanoma, and kidney cancer.”
For more information:
Topalian S. #CRA2509. Presented at: the 2012 American Society of Clinical Oncology Annual Meeting; June 1-5, 2012; Chicago.
Disclosure: This study was funded by Bristol-Myers Squibb.